Journal: NPJ Precision Oncology

Article Title: Metabolomic and transcriptomic profiling of HNSCC identifies AMIGO2 as a therapeutic target modulating tumor microenvironment

doi: 10.1038/s41698-025-01132-z

Figure Lengend Snippet: a Differential expression profiles of 31 purine metabolism regulators in normal ( n = 44) and HNSCC samples ( n = 509) from TCGA dataset. b Univariate Cox regression analysis of 23 purine metabolism regulators in TCGA and merge-GEO datasets. c Strategy for sequencing Fadu cells treated with AB680. d Heatmap showing the gene downregulation profile following AB680 treatment. e Biological pathway analysis of Fadu cells after AB680 treatment. f Schematic diagram of the screening strategy for potential receptor-ligand genes in cell-cell communication. g Bubble plot of receptor-ligand interactions between different epithelial cells and myofibroblast, INSR+ endothelial cells, and C1QA+ macrophages. Ns: no significant difference, * P < 0.05, ** P ≤ 0.01, *** P ≤ 0.001.

Article Snippet: In addition, to inhibit NT5E enzymatic activity, AB680 (MedChemExpress) was administered intraperitoneally at a dose of 20 mg/kg every four days, starting four days after tumor induction and continuing until the end of the experiment.

Techniques: Quantitative Proteomics, Sequencing

Journal: Frontiers in Immunology

Article Title: CD73: a new immune checkpoint for leukemia treatment

doi: 10.3389/fimmu.2025.1486868

Figure Lengend Snippet: Current studies targeting CD73 target therapy and combination therapy ( https://clinicaltrials.gov/ ).

Article Snippet: AB680| Zimberelimab| Nab-paclitaxel| Gemcitabine , Arcus Biosciences, Inc. , PHASE1 , NCT04104672.

Techniques:

Journal: Journal of Cancer Research and Clinical Oncology

Article Title: Targeting CD73 limits tumor progression and enhances anti-tumor activity of anti-PD-1 therapy in intrahepatic cholangiocarcinoma

doi: 10.1007/s00432-024-05869-1

Figure Lengend Snippet: Elevated CD73 expression of malignant cells in response to ICBs immunotherapy. ( A ) Schematic representation of the treatment schedule for anti-PD-1 monotherapy in AKT/NICD-induced spontaneous murine iCCAs. ( B ) Representative gross images and statistical results from AKT/NICD-induced murine iCCAs that received indicated treatments (6 mice for IgG and 5mice for anti-PD-1 treatment, 10 mg/kg). ( C ) scRNA-seq analysis of GSE151530 showing 12 iCCA biopsies from 10 patients collected at baseline or during ICBs therapy (PD-1 or PD-L1/CTLA-4). UMAP plot showing single cells distinguished by cell types and cell origins from different biopsy time points. ( D ) Volcano plot showing differentially expressed genes in malignant cells before and after ICBs treatment. ( E ) 40 genes that were upregulated in single malignant cells following ICBs therapy were associated with poor prognosis in both FU-iCCA Cohort and ICGC Cohort. ( F ) The drug-gene interaction database (DGIdb) database was used to identify the potential drug targets among the indicated genes. ( G ) Violin plot showing the expression levels of CD73 in different cell types in iCCA from GSE125449. ( H ) Immunohistochemical staining images showing CD73 expression in AKT/NICD iCCAs that received IgG or anti-PD-1 treatment. ( I ) Analysis of T cell dysfunction signature scores by TIDE algorithm in patients with high or low CD73 expression in FU-iCCA cohort. ( J ) Expression levels of CD73 between Non-Responsive versus Responsive (NR vs. R) samples to anti-PD-1 monotherapy in RCC cohort. Kaplan-Meier survival curves of OS for patients grouped by CD73 mRNA expression level in FU-iCCA cohort ( K ) and ICGC cohort ( L ), as well as CD73 protein levels in CCA protein cohort ( M ). ** P < 0.01; OS, overall survival; iCCA, intrahepatic cholangiocarcinoma

Article Snippet: For CD73 enzymatic activity inhibitor AB680 (MedChemExpress) administration, the stocks were dissolved in 100% DMSO.

Techniques: Expressing, Immunohistochemical staining, Staining

Journal: Journal of Cancer Research and Clinical Oncology

Article Title: Targeting CD73 limits tumor progression and enhances anti-tumor activity of anti-PD-1 therapy in intrahepatic cholangiocarcinoma

doi: 10.1007/s00432-024-05869-1

Figure Lengend Snippet: ICBs therapy upregulates CD73 expression in iCCA cells through TNF-α/NF-κB signaling pathway. ( A ) Evaluation of the effect of TNF-α and IFN-γ on CD73 mRNA expression in human iCCA cells CCLP1 and 9810 as determined by RT-PCR assays. ( B ) Evaluation of the effect of IFN-γ on CD73 protein expression in iCCA cells as detected by WB assays. ( C ) WB assays evaluating the effect of different concentrations of TNF-α on CD73 protein expression, as well as the downstream NF-κB signaling pathway in iCCA cells. ( D ) WB assays evaluating the effect of TNF-α on CD73 expression and NF-κB signaling in iCCA cells, with or without NF-κB pathway inhibitor BAY11-7082. WB, western blot; * P < 0.05, ** P < 0.01, *** P < 0.001

Article Snippet: For CD73 enzymatic activity inhibitor AB680 (MedChemExpress) administration, the stocks were dissolved in 100% DMSO.

Techniques: Expressing, Reverse Transcription Polymerase Chain Reaction, Western Blot

Journal: Journal of Cancer Research and Clinical Oncology

Article Title: Targeting CD73 limits tumor progression and enhances anti-tumor activity of anti-PD-1 therapy in intrahepatic cholangiocarcinoma

doi: 10.1007/s00432-024-05869-1

Figure Lengend Snippet: CD73 inhibitor AB680 synergizes with GC chemotherapy to inhibit CCLP1 tumor growth in vivo. ( A ) Establishment of the subcutaneous xenograft model with nude mice using sh-MOCK or CD73-knockdown CCLP1 cells. Growth curves ( B ), gross images ( C ), volumes and weight ( D ) of CCLP1 subcutaneous tumors from indicated groups. ( E ) Subcutaneous xenograft model with nude mice using vector or CD73-OE CCLP1 cells. Growth curves ( F ), gross images ( G ), volumes and weight ( H ) of CCLP1 subcutaneous tumors from indicated groups. ( I ) Subcutaneous CCLP1 tumor-bearing nude mice receiving PBS, Gem/Cis chemotherapy, CD73 inhibitor AB680, or combination therapy. Growth curves ( J ), gross images ( K ), volumes and weight ( L ) of CCLP1 tumors from indicated treatment groups. * P < 0.05, ** P < 0.01, *** P < 0.001

Article Snippet: For CD73 enzymatic activity inhibitor AB680 (MedChemExpress) administration, the stocks were dissolved in 100% DMSO.

Techniques: In Vivo, Knockdown, Plasmid Preparation

Journal: Journal of Cancer Research and Clinical Oncology

Article Title: Targeting CD73 limits tumor progression and enhances anti-tumor activity of anti-PD-1 therapy in intrahepatic cholangiocarcinoma

doi: 10.1007/s00432-024-05869-1

Figure Lengend Snippet: CD73 activates the AKT/GSK3β/β-catenin signaling pathway in iCCA cells via adenosine ( A ) Volcano plot showing differentially expressed genes in RBE cells transfected with shCD73 and shMOCK identified by RNA-seq analysis. ( B-C ) KEGG pathway analysis showing differential signaling pathways regulated by CD73 knockdown in RBE cells. ( D ) Gene set enrichment analysis (GSEA) showing that Hallmark gene sets Hypoxia, Inflammatory response, Glycolysis, Epithelial-mesenchymal transition pathways were enriched in shMOCK RBE cells compared with shCD73 cells. ( E ) Phosphorylation levels of AKT, GSK3β, and total β-catenin protein expression in the indicated iCCA cells as determined by WB assays. ( F ) Phosphorylation levels of AKT, GSK3β, and total β-catenin protein levels in CCLP1 cells treated with different concentrations of CD73 enzymatic activity inhibitor AB680 (left) or in 9810 cells under different concentrations of adenosine treatments (right) detected by WB assays

Article Snippet: For CD73 enzymatic activity inhibitor AB680 (MedChemExpress) administration, the stocks were dissolved in 100% DMSO.

Techniques: Transfection, RNA Sequencing Assay, Knockdown, Expressing, Activity Assay

Journal: Journal of Cancer Research and Clinical Oncology

Article Title: Targeting CD73 limits tumor progression and enhances anti-tumor activity of anti-PD-1 therapy in intrahepatic cholangiocarcinoma

doi: 10.1007/s00432-024-05869-1

Figure Lengend Snippet: CD73 inhibitor AB680 potentiates therapeutic efficacy of anti-PD-1 immunotherapy in murine iCCAs ( A ) Schematic representation of the schedule for anti-PD-1, CD73 inhibitor AB680, or combination therapy in AKT/NICD-induced murine iCCA model. ( B ) Body weight of tumor-bearing mice treated with vehicle + 10 mg/kg IgG, 10 mg/kg anti-PD-1, 10 mg/kg AB680, or the combination therapy. ( C ) Liver images from spontaneous iCCA models that received the indicated treatments (6 mice per group) at the indicated endpoint. ( D ) Representative IHC staining images for CK19 of liver sections from AKT/NICD-driven murine iCCAs from indicted groups. ( E ) Statistical analysis of liver weight to body weight ratios (LW/BW) and tumor nodule numbers in AKT-NICD injected mice * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001

Article Snippet: For CD73 enzymatic activity inhibitor AB680 (MedChemExpress) administration, the stocks were dissolved in 100% DMSO.

Techniques: Immunohistochemistry, Injection

Journal: Journal of Cancer Research and Clinical Oncology

Article Title: Targeting CD73 limits tumor progression and enhances anti-tumor activity of anti-PD-1 therapy in intrahepatic cholangiocarcinoma

doi: 10.1007/s00432-024-05869-1

Figure Lengend Snippet: CD73 inhibition combined with anti-PD-1 therapy transforms the immune landscape of the TME ( A ) The heatmap showing the normalized expression of 42 surface and intracellular immune markers in all 33 immune-cell subclusters. ( B ) t-SNE plots of tumor-infiltrating B cells, macrophages, CD8 + T cells, CD4 + T cells, NK cells, neutrophils, and dendritic cells in the AKT/NICD-induced spontaneous murine iCCAs identified by CyTOF analysis. ( C ) t-SNE plots showing the major tumor-infiltrating immune cell populations from the four treatment groups ( n = 4 per group). ( D ) t-SNE plots of tumor-infiltrating immune cells colored by the relative expression of corresponding lineage markers. ( E ) Stacked bar plots showing proportions of tumor-infiltrating immune cell populations identified by CyTOF analysis in each group. ( F ) Quantification of tumor-infiltrating B cells, macrophages, CD8 + T cells, CD4 + T cells, NK cells, neutrophils, and dendritic cells in AKT/NICD-induced iCCAs given the indicated treatment, assessed by CyTOF. ( G ) The expression level of indicated markers in tumor-infiltrating CD45 + immune cells among the four groups. * P < 0.05, ** P < 0.01; TME, tumor microenvironment

Article Snippet: For CD73 enzymatic activity inhibitor AB680 (MedChemExpress) administration, the stocks were dissolved in 100% DMSO.

Techniques: Inhibition, Expressing

Journal: Journal of Cancer Research and Clinical Oncology

Article Title: Targeting CD73 limits tumor progression and enhances anti-tumor activity of anti-PD-1 therapy in intrahepatic cholangiocarcinoma

doi: 10.1007/s00432-024-05869-1

Figure Lengend Snippet: Schematic diagram depicting the rationale for combination therapy with CD73 inhibitor AB680 and PD-1 blockade

Article Snippet: For CD73 enzymatic activity inhibitor AB680 (MedChemExpress) administration, the stocks were dissolved in 100% DMSO.

Techniques: